人表皮生长因子受体 2 (HER2) 在各种实体瘤类型中过度表达，可作为既定的治疗靶点。在过去三十年中，各种 HER2 靶向药物的快速发展，特别是抗体药物偶联物 (ADC) 的引入，显着提高了生存率。然而，抗 HER2 治疗的耐药性仍然构成严峻的挑战。 HER2 的复杂结构和动态二聚化特性给新型靶向治疗药物的开发带来了重大障碍。在这篇综述中，我们综合了对 HER2 复杂结构的最新见解，并对 HER2 靶向抗体及其衍生物的表位特征进行了前所未有的概述。此外，我们深入研究了抗 HER2 抗体结合表位及其各自功能之间的相关性，特别关注它们对耐药肿瘤的功效。此外，我们强调了针对特定位点或非重叠表位的新兴抗 HER2 药物的潜力，它们有望在可预见的未来改变 HER2 阳性肿瘤的治疗格局。版权所有 © 2024 Elsevier Ltd. 保留所有权利。

Human epidermal growth factor receptor-2 (HER2) is overexpressed in various solid tumor types, acting as an established therapeutic target. Over the last three decades, the fast-paced development of diverse HER2-targeted agents, notably marked by the introduction of the antibody-drug conjugate (ADC), yielding substantial improvements in survival rates. However, resistance to anti-HER2 treatments continues to pose formidable challenges. The complex structure and dynamic dimerization properties of HER2 create significant hurdles in the development of novel targeted therapeutics. In this review, we synthesize the latest insights into the structural intricacies of HER2 and present an unprecedented overview of the epitope characteristics of HER2-targeted antibodies and their derivatives. Furthermore, we delve into the correlation between anti-HER2 antibody binding epitopes and their respective functions, with a particular focus on their efficacy against resistant tumors. In addition, we highlight the potential of emerging anti-HER2 agents that target specific sites or non-overlapping epitopes, poised to transform the therapeutic landscape for HER2-positive tumors in the foreseeable future.Copyright © 2024 Elsevier Ltd. All rights reserved.